Cross-scale interactions between mineral and collagen for tendon-bone attachment

矿物质和胶原蛋白之间的跨尺度相互作用，用于腱骨附着

基本信息

批准号：
9342878
负责人：
Guy M Genin
金额：
$ 45.57万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-20 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9342878
关键词：
Age Anterior Cruciate Ligament Bone Tissue Clinical Collagen Collagen Fiber Collagen Fibril Communities Computer Simulation Crystallization Data Digit structure Elderly Electron energy loss spectroscopy Failure Fluorescence Foundations Future Geometry Goals Health Individual Lead Length Ligaments Maps Mechanics Methods Microscope Minerals Modeling Musculoskeletal Operative Surgical Procedures Outcome Pain Pathologic Phase Physiological Plant Roots Polarization Microscopy Population Raman Spectrum Analysis Resolution Rotator Cuff Scanning Source Stress Synchrotrons System Techniques Tendon structure Testing Tissue Engineering Tissue Model Tissues Transmission Electron Microscopy Work X ray diffraction analysis X-Ray Computed Tomography X-Ray Diffraction anterior cruciate ligament reconstruction base bone bone geometry bone healing clinical care clinical practice clinically relevant crosslink diffraction of light disability experimental study healing injured ligament injury mechanical properties millimeter multi-scale modeling musculoskeletal injury nanometer nanoscale novel older patient predictive modeling public health relevance repaired resilience response rotator cuff tear skeletal tool

项目摘要

DESCRIPTION (provided by applicant): Torn tendons and ligaments often require surgical repair to their bony insertions. A large percentage of these repairs have poor outcomes; for example, up to 94% of surgical rotator cuff repairs fail. At the root of these failures is the fundamental challenge of attaching two materials, tendon and bone, with vastly different mechanical properties. The natural tendon-to-bone insertion involves a number of mechanisms that create a strong and tough attachment. Unfortunately, this tissue degrades with age, and is not regenerated in healing. Our overall goal is to develop a multiscale model of the tendon-to-bone insertion that will lead to (1) tissue toughness metrics that can guide clinical decisions for elderly patients, and (2) foundations for future tissue- engineered surgical grafts. Based on our previous work, we hypothesize that toughening and strengthening mechanisms exist across several length scales, and that these are most pronounced in a the compliant region of tissue between tendon and bone that does not regrow in the healing setting. We will characterize the stiffening, strengthening, and toughening mechanisms that contribute to this resilience across scales in natural and pathologic tendon-to-bone insertions as a function of age. The work involves three aims: (1) At the nanoscale, elemental spatial maps will be acquired using transmission electron microscopy electron energy loss spectroscopy to determine mineral and collagen distributions across the insertion. Individual mineralized collagen fibrils will be mechanically tested; we have recently performed such tests on mammalian collagen fibrils. In silico experiments will identify and quantify deformation mechanisms underlying the toughness of mineralized collagen fibrils. (2) At the microscale, synchrotron X-ray diffraction, Raman spectroscopy, and polarized light microscopy will be used to determine the distributions of mineral content and collagen orientation. Mechanics of the tendon-to-bone insertion will be examined with micrometer resolution using a confocal microscope-mounted testing frame. In silico, nonlinear homogenization methods will be used to incorporate mineralized collagen fiber mechanics from Aim 1 into constitutive models of connected networks of mineralized and cross-linked collagen fibers. (3) At the millimeter scale, the 3D inter-digitation geometry of tendon and bone will be determined using phase contrast X-ray computed tomography and the mechanics of the tendon-to-bone insertion will be determined using tissue level tensile tests. In silico experiments combining tendon-to-bone geometry with microscale tissue models will produce hypotheses of mechanisms underlying tendon-to-bone insertion toughness. Mechanical fields will be passed down hierarchical model levels to evaluate collagen fibril response to predicted physiologic and pathologic tendon-to-bone insertion loading. Together, these models and data form the foundation of future tissue engineering efforts and efforts to identify clinically useful metrics of tendon-to-bone tissue health.

描述（由申请人提供）：肌腱和韧带撕裂通常需要手术修复其骨插入。这些维修的很大一部分的结果差。例如，多达94％的手术肩袖修理失败。这些故障的根源是将两种材料（肌腱和骨骼）附着的基本挑战，具有截然不同的机械性能。天然肌腱到骨的插入涉及多种机制，这些机制会产生强大而艰难的依恋。不幸的是，该组织随着年龄的增长而降解，并且在愈合中没有再生。我们的总体目标是开发肌腱到骨插入的多尺度模型，该模型将导致（1）组织韧性指标，该指标可以指导临床决策老年患者和（2）未来组织手术移植物的基础。基于我们以前的工作，我们假设在几个长度尺度上存在韧性和加强机制，并且在肌腱和骨骼之间的组织区域中最为明显，在愈合环境中不会再生长。我们将表征自然和病理肌腱对骨插入量表的僵化，增强和韧性机制，这些机制跨越了年龄的函数。这项工作涉及三个目的：（1）在纳米级，使用透射电子显微镜电子损失光谱法获取元素空间图，以确定整个插入的矿物质和胶原蛋白分布。单个矿化胶原纤维将进行机械测试；我们最近对哺乳动物胶原原纤维进行了此类测试。在计算机中，实验将识别和量化矿化胶原纤维韧性的背后的变形机制。（2）在显微镜，同步加速器X射线衍射，拉曼光谱和极化光显微镜将用于确定矿物含量和胶原方向的分布。肌腱到骨插入的力学将使用共聚焦显微镜安装的测试框架以微米分辨率进行检查。在计算机中，非线性均质化方法将用于将AIM 1的矿化胶原纤维力学纳入矿化和交联胶原蛋白纤维连接网络的组成型模型中。（3）在毫米尺度上，肌腱和将使用相对X射线计算机断层扫描确定骨头，并将使用组织水平的拉伸测试确定肌腱对骨插入的力学。在将肌腱到骨的几何形状与微观组织模型结合的硅实验中，将产生肌腱到骨插入韧性的机制的假设。机械场将被传递到分层模型水平，以评估对预测的生理和病理肌腱对骨插入负载的胶原原纤维反应。这些模型和数据共同构成了未来组织工程工作的基础，以及确定肌腱到骨组织健康的临床有用指标的努力。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Correction of bias in the estimation of cell volume fraction from histology sections.

DOI：
10.1016/j.jbiomech.2020.109705
发表时间：
2020-05-07
期刊：
Journal of biomechanics
影响因子：
2.4
作者：
Liu Y;Schwartz AG;Hong Y;Peng X;Xu F;Thomopoulos S;Genin GM
通讯作者：
Genin GM

In Situ Evaluation of Calcium Phosphate Nucleation Kinetics and Pathways during Intra- and Extrafibrillar Mineralization of Collagen Matrices.

DOI：
10.1021/acs.cgd.6b00864
发表时间：
2016
期刊：
CRYSTAL GROWTH & DESIGN
影响因子：
3.8
作者：
Kim, Doyoon;Lee, Byeongdu;Thomopoulos, Stavros;Jun, Young-Shin
通讯作者：
Jun, Young-Shin

Osmotic pressure induced tensile forces in tendon collagen.

DOI：
10.1038/ncomms6942
发表时间：
2015-01-22
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Masic, Admir;Bertinetti, Luca;Schuetz, Roman;Chang, Shu-Wei;Metzger, Till Hartmut;Buehler, Markus J.;Fratzl, Peter
通讯作者：
Fratzl, Peter

Nonlocal Effect on Stiffness Measurements of a Collagen Molecule.

对胶原分子刚度测量的非局部影响。